Position title: Assistant Professor
Phone: (608) 262-9730
Ph.D. in Biochemistry and Molecular Biology, University of Notre Dame
Our research interests lie in the area of synaptic function as related to the over-expression of amyloid beta protein precursor (APP) and amyloid beta in fragile X syndrome (FXS) and Alzheimer’s disease (AD). FXS is a devastating developmental disability that has profound effects on cognition, behavior and seizure susceptibility. There are currently no treatments that target the underlying cause of the disorder and recent clinical trials have failed. We are studying therapeutic and dietary approaches that modulate APP metabolite levels and rescue behavioral and biomarker phenotypes associated with FXS. This research is based on a seminal article that we published in 2007 in PLoS Biology demonstrating that APP is dysregulated in Fmr1KO mice through a metabotropic glutamate receptor 5 (mGluR5)-dependent pathway. This novel connection between a rare neurodevelopmental disorder (FXS) and a common neurodegenerative disorder (AD) raises the hypotheses that: (1) APP metabolites are potential therapeutic targets as well as biomarkers for FXS, and (2) mGluR5 inhibitors may be beneficial in the treatment of AD. Over the past decade, over 150 papers have cited and advanced the original finding that mGluR5 and fragile X mental retardation protein (FMRP) mediate the synthesis of APP (Molecular Neurobiolgy, 2019). Critical preclinical studies are needed to further validate APP metabolites as drug targets and biomarkers for FXS, and mGluR5 inhibitors as a therapeutic strategy for AD, to help propel these targets into clinical trials. During the course of chronic dosing of FXS and AD mice with mGluR5 inhibitors, we serendipitously discovered that diet significantly increases seizure propensity in the mice. Pursuit of these results led to studies in mice demonstrating that soy protein or a contaminant of soy promotes seizures, alters behavior and increases weight gain, and more so in developmental disability models. These findings have significant implications for babies who are fed soy-based infant formula. We pursued this original finding by utilizing the Simon’s Foundation Autism Research Initiative (SFARI) database of medical records to determine that autistic children fed a soy-based infant formula are more likely to exhibit seizures. Several ongoing projects in my laboratory are testing the effects of soy-based diets and contaminating agrochemicals on seizures, behavior and biomarkers in human and mouse models.
Fragile X syndrome, Alzheimer’s disease, mGluR5, diet, mouse models